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T Barbui

Publications and source records attributed to T Barbui.

At least 181 records · Page 10Linked to original sources
PubMed1991

Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients.

The efficacy of alternating vincristine, melphalan (M), cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP) polychemotherapy was compared with the M and prednisone (MP) regimen as induction treatment in multiple myeloma (MM). Three hundred four MM patients entered this study between March 1983 and July 1986; the analysis was performed in December 1989. The treatment groups did not show significant differences with respect to major prognostic factors. Median overall survival was 33.8 months. In the VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P less than .068) of the patients achieved an M component reduction greater than 50%. No significant difference was observed in the two treatment arms in terms of remission duration (21.3 v 19.6 months, P less than .66) and survival (31.6 v 37.0 months, P less than .28). Patients younger than 65 years did not show any advantage from the alternating polychemotherapy. At diagnosis, the plasma cell labeling index (LI) and serum beta-2 microglobulin (beta 2-m) were evaluated in 173 and 183 patients, respectively. A significantly reduced survival was observed for patients with LI greater than or equal to 2% (16.4 months) or beta 2-m greater than or equal to 6 mg/L (20.4 months). Even in these poor-risk subgroups, VMCP/VBAP was not superior to MP.

Aged↗
PubMed1991

Inherited protein C deficiency and nonhemorrhagic arterial stroke in young adults.

Out of a consecutive series of 50 young people less than 45 years old with nonhemorrhagic arterial stroke, three patients had inherited protein C deficiency. CT revealed hypodense areas consistent with the clinical picture, and angiography showed occlusion of some intracranial arterial vessels. Other possible associated causes of stroke were ruled out. One patient had a transient ischemic attack and a peripheral venous thrombosis prior to the actual stroke, whereas the others were completely asymptomatic, as were relatives with the same deficiency. We suggest determining protein C in ischemic stroke of all young adults, especially when major risk factors are excluded.

Adult↗
PubMed1991

Monoclonal lymphocytosis with villous lymphocytes: a chronic lymphoproliferative disease of CD11c+ B-cells.

Most of the circulating lymphocytes from three asymptomatic adults (one male, two female, age range 61-67 years) with isolated persistent lymphocytosis of between 7.1 and 10 x 10(9)/l possessed characteristic villous projections of the cell membrane. Morphological, histochemical, ultrastructural, immunological, and genotypic studies confirmed a clonal proliferation of tartrate-resistant acid phosphatase (TRAP)-negative CD5-CD10-CD25- and CD11c+ B-cells. In addition to CD11c, these cells expressed other adhesion receptors (LFA-1/CD11a, VLA-4/CD29/49d, ICAM-1/CD54, and LAM-1) and produced detectable amounts of interleukin-1 beta, interleukin-6, and in one case tumour necrosis factor-alpha mRNA. This monoclonal villous lymphocytosis (MVL) could be differentiated from B-cell chronic lymphocytic, prolymphocytic, and hairy cell leukaemias, and from previously recognized CD11c+ chronic B-cell leukaemia. A rare splenomegalic non-Hodgkin's lymphoma variant with circulating villous B-lymphocytes (SLVL), usually CD10+ and sometimes CD11c- and TRAP+, appears to be a closely related disorder. In all three patients the lymphocyte count increased very slowly, at a rate less than 5 x 10(9)/l per year, over 3-7.5 years of follow up, and a moderate splenomegaly eventually developed in one of the patients. Chemotherapy was never required. MVL may be a relatively benign clinical entity akin to SLVL within the group of CD11c+ B-cell lymphoproliferative disorders.

Aged↗
PubMed1991

MACOP-B for advanced stage large cell lymphoma (DLCL). More is better? Italian Multiregional Cooperative Study Group (IMCSGL).

A study of the predictive value for CR, DFS and OS of the presenting features was carried out on 180 patients with advanced stage DLCL treated with MACOP-B between June 1986 and March 1989. A multivariate regression analysis identified LDH level, bone marrow involvement and tumor burden as independent risk factors with a 4 year survival rate of 79%, 58% and 28% respectively. Therefore MACOP-B proved to be an adequate treatment for the first two groups of patients but not for the third which requires a more aggressive treatment. A sequential single drug high dose chemotherapy with collection of peripheral blood stem cell program followed by bone marrow harvesting, super-intensive radio-chemotherapy and bone marrow transplant has been activated. Seven patients have been so far enrolled: preliminary results demonstrated the feasibility of the program. A larger number of cases and a longer follow-up is required for assessing the efficacy of this approach.

Adolescent↗
PubMed1990

Expression of leukocyte alkaline phosphatase gene in normal and leukemic cells: regulation of the transcript by granulocyte colony-stimulating factor.

The levels of leukocyte alkaline phosphatase (LAP) messenger RNA (mRNA) are evaluated in B and T lymphocytes, monocytes, and polymorphonuclear cells (PMNs), and this transcript is found to be present only in PMNs. Precursors of the myelomonocytic pathway, represented by leukemic cells isolated from several cases of chronic myelogenous leukemia (CML) in its stable and blastic phase and acute myelogenous leukemia (AML), are devoid of LAP transcript. These data support the notion that LAP is a marker of the granulocyte terminal differentiation. Despite the absence of LAP mRNA in both the myeloid and the lymphoid precursors, nuclear run-on experiments show constitutive transcription of the LAP gene in leukemic cells obtained from AML, CML, as well as acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia (B-CLL). In CML and in chronic myelo-monocytic leukemia (CMML) PMNs, granulocyte colony-stimulating factor (G-CSF) specifically accumulates LAP mRNA without showing a substantial increase in the rate of transcription of the LAP gene. Once increased by G-CSF, LAP mRNA is very stable, showing a half-life of more than 4 hours in the presence of actinomycin-D. G-CSF is suggested to play a pivotal role in the modulation of LAP transcript in PMNs.

Alkaline Phosphatase↗
PubMed1990

A frameshift mutation leading to type 1 antithrombin deficiency and thrombosis.

Type 1 antithrombin III (ATIII) deficiency, which is the commonest form of inherited ATIII defect, is characterized by a quantitative reduction in both immunologically and functionally detectable protein. This condition is associated with a high incidence of thromboembolic disorder. Previous investigations have shown that the ATIII genes in the majority of cases are grossly intact, but the precise underlying molecular defects remain unknown. We have investigated the molecular basis of a type 1 ATIII deficiency in an Italian kindred by enzymatic amplification of the ATIII gene sequences in affected family members and direct sequencing of the amplified genomic DNA. A novel mutation, the deletion of a single T in the second position of codon 119, was identified in each of the affected individuals. The resulting frameshift leads to a premature termination in codon 126, effectively resulting in a null allele.

Adult↗
PubMed1990

Interleukin-1 and interleukin-2 control granulocyte- and granulocyte-macrophage colony-stimulating factor gene expression and cell proliferation in cultured acute myeloblastic leukemia.

In vitro proliferation of leukemic cells purified from 10 cases of acute myeloblastic leukemia (AML) was analyzed in basal conditions or in the presence of exogenous recombinant (r) Interleukin (IL) 1. In parallel, blasts from 5 of these patients were studied for granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF) mRNA. IL-1 augmented the spontaneous AML cell proliferation in all cases and induced de novo expression or increased amounts of GM-CSF and/or G-CSF transcripts in 4 of the 5 cases evaluated. IL-1-induced AML cell proliferation was modulated by neutralizing anti-GM-CSF or anti-G-CSF antibodies in those cases in which CSF mRNAs were induced or increased by exogenous cytokine. In the same cases, biosynthetic labelling and immunoprecipitation studies using monospecific anti-GM-CSF antibodies showed that IL-1 also increased the levels of GM-CSF protein synthesis. Addition of neutralizing anti-IL-1 antibodies to AML cell cultures completely abolished ongoing GM-CSF synthesis, suggesting that endogenous IL-1 is needed to maintain autocrine production of CSFs. The effects of rIL-2 were investigated in a larger series of 21 patients. The cytokine reduced spontaneous AML cell proliferation in 8 cases. It caused complete disappearance of GM-CSF mRNA in 1 case, and marked reduction of G-CSF mRNA in 2 cases. Increased AML cell proliferation was observed in 2 of 21 cases. These findings suggest that expression of CSF genes and cell proliferation in AML are under the control of different cytokines acting in autocrine or paracrine fashion.

Antibodies↗
PubMed1990

Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor.

The binding of affinity-purified anticardiolipin antibodies (ACA) to liposomes that contained cardiolipin or phosphatidylserine was investigated. ACA bound to these liposomes only in the presence of plasma or serum, which indicated a requirement for a plasma component. This component--referred to as aca-cofactor--was purified; its activity to support ACA binding to liposomes that contained cardiolipin was not destroyed by heat (10 min at 90 degrees C), but was greatly diminished on incubation with trypsin. aca-cofactor bound liposomes that contained negatively charged phospholipid but had no affinity for liposomes that contained neutral phospholipid (eg, phosphatidylcholine); this binding was independent of calcium ions. aca-cofactor was essential for ACA to bind to liposomes that contained cardiolipin or phosphatidylserine and, when coated on a microtitre plate in the absence of any phospholipid, aca-cofactor was an apparent antigen for ACA in an enzyme-linked immunosorbent assay. aca-cofactor is a single chain polypeptide with an apparent molecular weight of 50 kD (non-reduced), which increases to 70 kD upon reduction, and its properties closely resemble those of beta 2-glycoprotein I (apolipoprotein H).

Adult↗
PubMed1990

Early deaths and anti-hemorrhagic treatments in acute promyelocytic leukemia. A GIMEMA retrospective study in 268 consecutive patients.

The records of 268 consecutive patients with acute hypergranular promyelocytic leukemia, treated at 29 Italian centers between January 1984 and December 1987, have been reviewed to assess the incidence of early hemorrhagic deaths and the effectiveness of various antihemorrhagic treatments. Three separate groups were considered: 94 patients were treated with heparin, 67 with anti-fibrinolytics (tranexamic acid, epsilon-aminocaproic acid, or aprotinin), and 107 with supportive therapy alone. The overall incidence of early hemorrhagic death (within the first 10 days of treatment) was 9.4%, with no significant differences between the various groups. Similarly, there were no differences in complete remission rates or duration of survival. The consumption of packed red blood cells and platelet concentrates was similar for two of the groups, and there was a significantly greater use of platelet concentrates for heparin-treated patients. High blast cell counts on the day of admission were significantly associated with hemorrhagic death within the first 10 days. These counts, plus high blast cell counts and low platelet counts, were associated with death within 24 hours.

Adolescent↗
PubMed1990

Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study.

Lymphoproliferative disease of granular lymphocytes (LDGL) is a recently recognized, relatively rare atypical lymphocytosis characterized by the presence of over 2000 lymphocytes with cytoplasmic azurophilic granules/mm3 in the peripheral blood. The clinical course is heterogeneous, varying from spontaneous regression to progressive, malignant disease. As a consequence, clinical intervention is not standardized. In a worldwide multicenter study, the authors observed 151 patients with LDGL for a mean follow-up time of 29 months. Forty-three patients were asymptomatic at the time of diagnosis. In the remaining cases, clinical symptoms included fever (41 cases), infections (58), neutropenia (47), anemia (17), and thrombocytopenia (12). In 69 cases, LDGL coexisted with an associated disease. Most patients had a nonprogressive clinical course despite the presence of severe symptoms. In 19 patients, death related to LDGL occurred within 48 months. The authors investigated which features at diagnosis were significantly associated with increased mortality. In the univariate analysis, lymph node and liver enlargement, fever at presentation, skin infiltration, a low (less than or equal to 5000/mm3) or high (greater than 20,000/mm3) peripheral leukocyte count, relatively low (less than or equal to 3000) or high (greater than 7000/mm3) absolute peripheral granular lymphocyte (GL) count, and a low (less than or equal to 15%) percentage of HNK-1-positive cells were found to be predictors of increased mortality. In the multivariate analysis, significant independent predictors were fever at diagnosis, a low (less than or equal to 15%) percentage of HNK-1-positive peripheral blood mononuclear cells (PBMC) and a relatively low (less than or equal to 3000) GL count. These results showed that about 25% of the patients with LDGL were diagnosed after a routine blood count and had no clinical symptoms. The remaining patients were symptomatic, with some experiencing a fatal clinical course. The author's analysis of the significant prognostic features of LDGL may help in understanding the heterogeneous nature of this syndrome.

Adolescent↗
PubMed1990

Cytotoxicity and DNA damage caused by 4-demethoxydaunorubicin and its metabolite 4-demethoxy-13-hydroxydaunorubicin in human acute myeloid leukemia cells.

4-Demethoxydaunorubicin (4-DMDR) and its major metabolite 4-demethoxy-13-hydroxydaunorubicin (4-DMDRol) were investigated for their cytotoxicity and mode of action against human leukemic cells. The drug and its metabolite appeared to be equally potent as both inhibitors of cell proliferation and inducers of DNA double-strand breaks in the OCI AML-3 cell line and cells derived directly from patients with acute myeloid leukemia (AML). This suggests that 4-DMDRol plays an important role in the antileukemic activity of 4-DMDR.

Adult↗
PubMed1990

Hemostatic complications in young patients with essential thrombocythemia.

PURPOSE: The purpose of this study was to determine the incidence of hemostastic complications in young patients with essential thrombocythemia (ET). PATIENTS AND METHODS: The clinical course of 44 patients under the age of 45 with the diagnosis of ET was reviewed in a retrospective manner. Patients were collected from three medical centers in the United States and Italy: the Brigham and Women's Hospital and the Harvard Community Health Plan, Boston, Massachusetts, and the Ospedali Riuniti di Bergamo, Bergamo, Italy. RESULTS: The overall incidence of hemorrhage or thrombosis, or both, in this group of patients was 39% (17 of 44), with serious complications occurring in 23% (10 of 44). Two patients died of thrombotic events. Neither the presence of symptoms at diagnosis nor any single laboratory parameter proved predictive of clinical sequelae. Treatment with antiplatelet drugs or platelet-lowering agents was not protective. CONCLUSION: We conclude that ET in young patients may result in serious and life-threatening hemostatic problems and consequently that young age is not a favorable prognostic factor in this disease.

Adolescent↗
PubMed1990

High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia.

In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables.

Adolescent↗
PubMed1990

Association of NK-cell lymphoproliferative disease and nephrotic syndrome.

A 56-year-old white man with a seven-year history of lymphocytosis of large granular lymphocytes (LGL) developed mild renal insufficiency (serum creatinine 150 mumol/L (1.7 mg/dL) with proteinuria (3.4 g/day). Laboratory investigations confirmed a proliferative disease of non-T lineage cytotoxic LGL/natural killer (NK) cells, and the renal biopsy documented focal and segmental glomerulosclerosis associated with interstitial inflammation and tubular atrophy. These findings could be explained by production and release of humoral mediators by pathologic LGL/NK cells. The renal function must be carefully monitored in patients with LGL/NK proliferative disorders, and the role of the NK cell system in renal diseases should be investigated.

Biopsy↗